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Adv Pharm Bull. 2019;9(3): 445-452.
doi: 10.15171/apb.2019.053
PMID: 31592109
PMCID: PMC6773943
Scopus ID: 85070477465
  Abstract View: 631
  PDF Download: 404

Research Article

Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation

Edy Meiyanto 1,2 * ORCID logo, Herwandhani Putri 2, Yonika Arum Larasati 2 ORCID logo, Rohmad Yudi Utomo 1,2 ORCID logo, Riris Istighfari Jenie 1 ORCID logo, Muthi Ikawati 1 ORCID logo, Beni Lestari 2,3 ORCID logo, Noriko Yoneda-Kato 3, Ikuko Nakamae 3, Masashi Kawaichi 4, Jun-Ya Kato 3

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281 Indonesia.
2 Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281 Indonesia.
3 Laboratory of Tumor Cell Biology, Nara Institute of Science and Technology, Japan.
4 Laboratory of Gene Function in Animals, Nara Institute of Science and Technology, Japan.

Abstract

Purpose: Pentagamavunon-1 (PGV-1) is a curcumin analogue that shows cytotoxic activity in various cancer cells. In this study, we evaluated the effect of PGV-1 on a highly metastatic breast cancer cell line, the 4T1 cells, as an anti-metastatic and anti-proliferative agent.

Methods: Cell viability was evaluated using MTT assay; while cell cycle profile, apoptosis incidence, and ROS intracellular level were determined by flow cytometry. Cell senescence was observed under senescence-associated-β-galactosidase (SA-β-gal) staining assay. The expression of matrixmetalloproteinase-9 (MMP-9) was determined using immunoreaction based-ELISA, while other proteins expression were detected using immunoblotting.

Results: Curcumin and PGV-1 showed cytotoxic effects on 4T1 cells with IC50 value of 50 and 4 µM, respectively. The cytotoxic activity of PGV-1 was correlated to the induction of G2/M cell cycle arrest and cell senescence. Furthermore, PGV-1 increased the accumulation of intracellular ROS level. We also revealed that PGV-1 bound to several ROS-metabolizing enzymes, including glyoxalase I (GLO1), peroxiredoxin 1 (PRDX1), N-ribosyldihydronicotinamide: quinone reductase 2 (NQO2), aldo-keto reductase family 1 member c1 (AKR1C1). As an antimetastatic agent, PGV-1 showed less inhibitory effect on cell migration compared to curcumin. However, PGV-1 significantly decreased MMP-9 protein expression in a dose-dependent manner suggesting it still potent to inhibit metastatic cells.

Conclusion: Overall, our findings suggest that PGV-1 is potential to be developed as an antiproliferative and anti-metastatic agent.

Keywords: Anti-proliferative, Metastatic inhibitor, PGV-1 (curcumin analogoe), Reactive oxygen species (ROS), The 4T1 cells
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Submitted: 04 Oct 2018
Revision: 08 Jan 2019
Accepted: 14 Apr 2019
ePublished: 01 Aug 2019
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